Wu Chunhui, Li Dan, Wang Lianhui, Guan Xiaotian, Tian Yuan, Yang Hong, Li Shun, Liu Yiyao
Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, PR China; Center for Information in BioMedicine, University of Electronic Science and Technology of China, Chengdu 610054, PR China; Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu 610054, PR China.
Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, PR China.
Acta Biomater. 2017 Apr 15;53:631-642. doi: 10.1016/j.actbio.2017.01.078. Epub 2017 Feb 1.
UNLABELLED: Light-triggered nanotheranostics opens a fascinating but challenging avenue to achieve simultaneous and highly efficient anticancer outcomes for multimodal therapeutic and diagnostic modalities. Herein, a multifunctional phototheranostics based on a photosensitizer-assembled graphene/gold nanostar hybrid (GO/AuNS-PEG) was developed for cancer synergistic photodynamic (PDT) and photothermal therapy (PTT) as well as effective photothermal imaging. The stable and biocompatible GO/AuNS-PEG composite displayed a high photothermal conversion efficiency due to the enhanced optical absorbance of both graphene and gold nanostars in the near-infrared (NIR) range. By tuning the absorption wavelength of GO/AuNS-PEG to that of Chlorin e6 (Ce6), GO/AuNS-PEG/Ce6 completely eliminated the EMT6 xenograft tumors by the tremendous synergistic anticancer efficiency of simultaneous PDT and PTT under a single NIR laser irradiation (660nm) in vivo. The underlying mechanism may be the enhanced cytoplasmic uptake and accumulation of GO/AuNS-PEG/Ce6 and the subsequent photodestruction of the lysosomal membrane and mitochondria. Moreover, GO/AuNS-PEG/Ce6 exhibited negligible side-effects on the body and other organs. These results demonstrate that the graphene/gold nanostar nanoconstruct provides a versatile and reliable integrated platform for the photo-controlled cancer theragnostic applications. STATEMENT OF SIGNIFICANCE: This work demonstrated the application of graphene-Au Nanostars hybridized system (denoted as GO/AuNS-PEG) in single wavelength laser induced synergistic photodynamic (PDT) and photothermal therapy (PTT) and effective cancer photothermal/fluorescence multimode imaging. GO/AuNS-PEG showed excellent biocompatibility and high dual-enhanced photothermal efficiency under the near-infrared laser irradiation that was very promise for deep tumor imaging. By combining with the photosensitizer Chlorin e6, both in vitro and in vivo data confirmed the efficient photoablation of the EMT6 tumors through the synergistic PDT and PTT effect under the activation of a single wavelength laser.
未标记：光触发纳米诊疗技术为实现多模态治疗和诊断方式的同步且高效抗癌效果开辟了一条引人入胜但具有挑战性的途径。在此，我们开发了一种基于光敏剂组装的石墨烯/金纳米星杂化物（GO/AuNS-PEG）的多功能光诊疗剂，用于癌症的协同光动力疗法（PDT）和光热疗法（PTT）以及有效的光热成像。由于石墨烯和金纳米星在近红外（NIR）范围内的光吸收增强，稳定且生物相容的GO/AuNS-PEG复合材料表现出高光热转换效率。通过将GO/AuNS-PEG的吸收波长调至叶绿素e6（Ce6）的吸收波长，GO/AuNS-PEG/Ce6在体内单一近红外激光照射（660nm）下，通过同时进行PDT和PTT的巨大协同抗癌效率，完全消除了EMT6异种移植肿瘤。其潜在机制可能是GO/AuNS-PEG/Ce6的胞质摄取和积累增强，以及随后溶酶体膜和线粒体的光破坏。此外，GO/AuNS-PEG/Ce6对身体和其他器官的副作用可忽略不计。这些结果表明，石墨烯/金纳米星纳米结构为光控癌症诊疗应用提供了一个通用且可靠的集成平台。 重要性声明：本工作展示了石墨烯-金纳米星杂交系统（记为GO/AuNS-PEG）在单波长激光诱导的协同光动力疗法（PDT）和光热疗法（PTT）以及有效的癌症光热/荧光多模态成像中的应用。GO/AuNS-PEG在近红外激光照射下表现出优异的生物相容性和高双重增强光热效率，这对深部肿瘤成像非常有前景。通过与光敏剂叶绿素e6结合，体外和体内数据均证实，在单一波长激光激活下，通过协同PDT和PTT效应可有效光消融EMT6肿瘤。
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